keyword
https://read.qxmd.com/read/38607302/sers-in-3d-cell-models-a-powerful-tool-in-cancer-research
#1
REVIEW
Lara Troncoso-Afonso, Gail A Vinnacombe-Willson, Clara García-Astrain, Luis M Liz-Márzan
Unraveling the cellular and molecular mechanisms underlying tumoral processes is fundamental for the diagnosis and treatment of cancer. In this regard, three-dimensional (3D) cancer cell models more realistically mimic tumors compared to conventional 2D cell cultures and are more attractive for performing such studies. Nonetheless, the analysis of such architectures is challenging because most available techniques are destructive, resulting in the loss of biochemical information. On the contrary, surface-enhanced Raman spectroscopy (SERS) is a non-invasive analytical tool that can record the structural fingerprint of molecules present in complex biological environments...
April 12, 2024: Chemical Society Reviews
https://read.qxmd.com/read/38562906/discovery-of-a-cell-active-chikungunya-virus-nsp2-protease-inhibitor-using-a-covalent-fragment-based-screening-approach
#2
Eric M Merten, John D Sears, Tina M Leisner, Paul B Hardy, Anirban Ghoshal, Mohammad Anwar Hossain, Kesatebrhan Haile Asressu, Peter J Brown, Michael A Stashko, Laura E Herring, Angie L Mordant, Thomas S Webb, Christine A Mills, Natalie K Barker, Jamie J Arnold, Craig E Cameron, Daniel N Streblow, Nathaniel J Moorman, Mark Heise, Timothy M Willson, Konstantin I Popov, Kenneth H Pearce
UNLABELLED: Chikungunya virus (CHIKV) is a mosquito-borne alphavirus that has been responsible for numerous large-scale outbreaks in the last twenty years. Currently, there are no FDA-approved therapeutics for any alphavirus infection. CHIKV non-structural protein 2 (nsP2), which contains a cysteine protease domain, is essential for viral replication, making it an attractive target for a drug discovery campaign. Here, we optimized a CHIKV nsP2 protease (nsP2pro) biochemical assay for the screening of a 6,120-compound cysteine-directed covalent fragment library...
March 22, 2024: bioRxiv
https://read.qxmd.com/read/38559077/location-of-ryanodine-receptor-type-2-mutation-predicts-age-of-onset-of-sudden-death-in-catecholaminergic-polymorphic-ventricular-tachycardia-a-systematic-review-and-meta-analysis-of-case-based-literature
#3
Halil Beqaj, Leah Sittenfeld, Alexander Chang, Marco Miotto, Haikel Dridi, Gloria Willson, Carolyn Martinez Jorge, Jaan Altosaar Li, Steven Reiken, Yang Liu, Zonglin Dai, Andrew R Marks
BACKGROUND: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a rare inherited arrhythmia caused by mutations in the ryanodine receptor type 2 (RyR2). Diagnosis of CPVT often occurs after a major cardiac event, thus posing a severe threat to the patient's health. METHODS: Publication databases, including PubMed, Scopus, and Embase, were searched for articles on patients with RyR2-CPVT mutations and their associated clinical presentation. Articles were reviewed by two independent reviewers and mutations were analyzed for demographic information, mutation distribution, and therapeutics...
March 16, 2024: medRxiv
https://read.qxmd.com/read/38525075/the-efficient-synthesis-and-purification-of-2-3-cgamp-from-escherichia-coli
#4
JOURNAL ARTICLE
Rohan Kulkarni, Vijay Maranholkar, Nam Nguyen, Patrick C Cirino, Richard C Willson, Navin Varadarajan
Agonists of the stimulator of interferon genes (STING) pathway are being explored as potential immunotherapeutics for the treatment of cancer and as vaccine adjuvants for infectious diseases. Although chemical synthesis of 2'3' - cyclic Guanosine Monophosphate-Adenosine Monophosphate (cGAMP) is commercially feasible, the process results in low yields and utilizes organic solvents. To pursue an efficient and environmentally friendly process for the production of cGAMP, we focused on the recombinant production of cGAMP via a whole-cell biocatalysis platform utilizing the murine cyclic Guanosine monophosphate-Adenosine monophosphate synthase (mcGAS)...
2024: Frontiers in Microbiology
https://read.qxmd.com/read/38492276/platinum-chemotherapy-for-early-triple-negative-breast-cancer
#5
REVIEW
Sofia Re Mason, Melina L Willson, Sam J Egger, Jane Beith, Rachel F Dear, Annabel Goodwin
BACKGROUND: Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer associated with shorter survival and a higher likelihood of recurrence. In early TNBC, platinum chemotherapy has been shown to improve pathological complete response (pCR); however, its effect on long-term survival outcomes has not been fully elucidated. METHODS: Randomised controlled trials examining neoadjuvant or adjuvant platinum chemotherapy for early TNBC were included...
March 12, 2024: Breast: Official Journal of the European Society of Mastology
https://read.qxmd.com/read/38491305/differential-in-vivo-roles-of-mpl-cytoplasmic-tyrosine-residues-in-murine-hematopoiesis-and-myeloproliferative-disease
#6
JOURNAL ARTICLE
Kira Behrens, Maria Kauppi, Elizabeth M Viney, Andrew J Kueh, Craig D Hyland, Tracy A Willson, Liam Salleh, Carolyn A de Graaf, Jeffrey J Babon, Marco J Herold, Nicos A Nicola, Warren S Alexander
Thrombopoietin (Tpo), which binds to its specific receptor, the Mpl protein, is the major cytokine regulator of megakaryopoiesis and circulating platelet number. Tpo binding to Mpl triggers activation of Janus kinase 2 (Jak2) and phosphorylation of the receptor, as well as activation of several intracellular signalling cascades that mediate cellular responses. Three tyrosine (Y) residues in the C-terminal region of the Mpl intracellular domain have been implicated as sites of phosphorylation required for regulation of major Tpo-stimulated signalling pathways: Mpl-Y565, Mpl-Y599 and Mpl-Y604...
March 15, 2024: Leukemia
https://read.qxmd.com/read/38471229/dietary-inclusion-of-a-saccharomyces-cerevisiae-metabolite-improved-reproductive-performance-but-did-not-affect-intestinal-permeability-in-two-chicken-meat-breeder-lines
#7
JOURNAL ARTICLE
Rebecca Ea Forder, Nicky-Lee Willson, Joshua A Angove, Todd J McWhorter, Matthew A McQueen, David J Cadogan
Gastrointestinal dysbiosis is a disturbance in mucosal homeostasis, producing low-grade chronic intestinal inflammation and impaired intestinal barrier function. It is induced by several factors, including nutrition and stress, which are both significant factors when considering current broiler breeder practices. A great grandparent (GGP) chicken meat line was identified displaying clinical signs characteristic of potential dysbiosis, including wet droppings and litter, in addition to reduced reproductive performance when compared to a consistently high performing line...
February 27, 2024: Poultry Science
https://read.qxmd.com/read/38345529/two-part-phase-1-study-to-evaluate-the-taste-profile-of-novel-belumosudil-oral-suspensions-and-assess-the-relative-bioavailability-and-food-effect-of-the-selected-belumosudil-oral-suspension-compared-with-oral-tablet-reference-in-healthy-male-participants
#8
JOURNAL ARTICLE
Olivier Schueller, Galit Regev, Nand Singh, Ashley Willson, Mark Beville, Nazim Kanji, Lauren Lohmer, Jeegar Patel
Belumosudil is a selective rho-associated coiled-coil-containing protein kinase 2 inhibitor in clinical use for the treatment of chronic graft-versus-host disease. The current tablet formulation may be inappropriate for children or adults with dysphagia and/or upper gastrointestinal manifestations of chronic graft-versus-host disease. This study (NCT04735822) assessed the taste and palatability of oral suspensions of belumosudil, evaluated the relative bioavailability of an oral suspension versus the tablet formulation, and characterized the effect of food on the pharmacokinetics of an oral suspension...
February 12, 2024: Clinical Pharmacology in Drug Development
https://read.qxmd.com/read/38218213/illuminating-function-of-the-understudied-druggable-kinome
#9
REVIEW
Shawn M Gomez, David H Drewry, Timothy M Willson, Michael B Major, Reid R Townsend, Peter K Sorger, Gary L Johnson
The human kinome, with more than 500 proteins, is crucial for cell signaling and disease. Yet, about one-third of kinases lack in-depth study. The Data and Resource Generating Center for Understudied Kinases has developed multiple resources to address this challenge including creation of a heavy amino acid peptide library for parallel reaction monitoring and quantitation of protein kinase expression, use of understudied kinases tagged with a miniTurbo-biotin ligase to determine interaction networks by proximity-dependent protein biotinylation, NanoBRET probe development for screening chemical tool target specificity in live cells, characterization of small molecule chemical tools inhibiting understudied kinases, and computational tools for defining kinome architecture...
January 11, 2024: Drug Discovery Today
https://read.qxmd.com/read/38213874/the-plasticity-of-immune-cell-response-complicates-dissecting-the-underlying-pathology-of-multiple-sclerosis
#10
REVIEW
Sujan Kumar Sarkar, Annie M L Willson, Margaret A Jordan
Multiple sclerosis (MS) is a neurodegenerative autoimmune disease characterized by the destruction of the myelin sheath of the neuronal axon in the central nervous system. Many risk factors, including environmental, epigenetic, genetic, and lifestyle factors, are responsible for the development of MS. It has long been thought that only adaptive immune cells, especially autoreactive T cells, are responsible for the pathophysiology; however, recent evidence has indicated that innate immune cells are also highly involved in disease initiation and progression...
2024: Journal of Immunology Research
https://read.qxmd.com/read/38136325/in-vitro-three-dimensional-3d-models-for-melanoma-immunotherapy
#11
REVIEW
Gemma Nomdedeu-Sancho, Anastasiya Gorkun, Naresh Mahajan, Kelsey Willson, Cecilia R Schaaf, Konstantinos I Votanopoulos, Anthony Atala, Shay Soker
Melanoma is responsible for the majority of skin cancer-related fatalities. Immune checkpoint inhibitor (ICI) treatments have revolutionized the management of the disease by significantly increasing patient survival rates. However, a considerable number of tumors treated with these drugs fail to respond or may develop resistance over time. Tumor growth and its response to therapies are critically influenced by the tumor microenvironment (TME); it directly supports cancer cell growth and influences the behavior of surrounding immune cells, which can become tumor-permissive, thereby rendering immunotherapies ineffective...
December 9, 2023: Cancers
https://read.qxmd.com/read/38044474/lower-extremity-joint-contact-force-symmetry-during-walking-and-running-2-7-years-post-acl-reconstruction
#12
JOURNAL ARTICLE
Ankur Anand Padhye, Stacey A Meardon, Anthony Kulas, John Willson
Premature osteoarthritis after anterior cruciate ligament reconstruction (ACLR) is common among athletes. Reduced knee contact forces after ACLR likely contribute to the multifactorial etiology of the disease. Whether this reduction is accompanied by compensatory increases in joint contact forces (JCF) at adjacent or contralateral joints is unclear. It is also unclear if compensatory effects depend on the task demands. Thus, we compared hip, knee, and ankle JCF symmetry between individuals with reconstruction and a matched control group during walking and running...
December 3, 2023: Journal of Orthopaedic Research: Official Publication of the Orthopaedic Research Society
https://read.qxmd.com/read/38027884/seroprevalence-of-hepatitis-e-virus-hev-among-male-craft-and-manual-workers-in-qatar-2020-2021
#13
JOURNAL ARTICLE
Nadin Younes, Hadi M Yassine, Parveen Banu Nizamuddin, Katerina Kourentzi, Patrick Tang, Houssein H Ayoub, Makiyeh Khalili, Peter V Coyle, Dmitri Litvinov, Richard C Willson, Laith J Abu-Raddad, Gheyath K Nasrallah
BACKGROUND: The rapid growth of Qatar in the last two decades has attracted a large influx of immigrant craft and manual workers (CMWs) seeking employment in jobs associated with food handling, domestic service, and construction. Nearly 60 % of Qatar's population are expatriates CMWs, including many from hyperendemic countries for HEV. Thus, estimating the seroprevalence of HEV in Qatar and understanding its epidemiology is essential for public health efforts to control HEV transmission in Qatar...
November 2023: Heliyon
https://read.qxmd.com/read/37805097/the-effect-of-frontal-deformity-at-the-ankle-joint-on-total-ankle-arthroplasty-revision-rate
#14
JOURNAL ARTICLE
Caroline J Ko, Zachary Brooks, Raddison Veater, Shiyun Zhu, Kyle W Willson, Danny J Choung
The presence of severe coronal plane deformity in the ankle joint is widely recognized as challenging to correct by total ankle joint arthroplasty alone, necessitating additional rearfoot fusion. The primary aim of this retrospective study was to investigate the potential associations between the presence or severity of coronal tibiotalar deformities and adverse outcomes after isolated total ankle arthroplasty, such as revisions and complications. The secondary aim was to analyze the potential associations between comorbidities, demographics, and implant types, and adverse outcomes...
October 5, 2023: Journal of Foot and Ankle Surgery
https://read.qxmd.com/read/37681577/platinum-based-chemotherapy-for-early-triple-negative-breast-cancer
#15
REVIEW
Sofia Re Mason, Melina L Willson, Sam J Egger, Jane Beith, Rachel F Dear, Annabel Goodwin
BACKGROUND: Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer associated with shorter survival and a higher likelihood of the cancer returning. In early TNBC, platinum-based chemotherapy has been shown to improve pathological complete response (pCR); however, its effect on long-term survival outcomes has not been fully elucidated and recommendations to include platinum chemotherapy are not consistent in international guidelines. OBJECTIVES: To evaluate the benefits and harms of platinum-based chemotherapy as adjuvant and neoadjuvant treatment in people with early triple-negative breast cancer...
September 8, 2023: Cochrane Database of Systematic Reviews
https://read.qxmd.com/read/37634194/investigation-of-the-host-kinome-response-to-coronavirus-infection-reveals-pi3k-mtor-inhibitors-as-betacoronavirus-antivirals
#16
JOURNAL ARTICLE
Ethan J Fritch, Angie L Mordant, Thomas S K Gilbert, Carrow I Wells, Xuan Yang, Natalie K Barker, Emily A Madden, Kenneth H Dinnon, Yixuan J Hou, Longping V Tse, Izabella N Castillo, Amy C Sims, Nathaniel J Moorman, Premkumar Lakshmanane, Timothy M Willson, Laura E Herring, Lee M Graves, Ralph S Baric
Host kinases play essential roles in the host cell cycle, innate immune signaling, the stress response to viral infection, and inflammation. Previous work has demonstrated that coronaviruses specifically target kinase cascades to subvert host cell responses to infection and rely upon host kinase activity to phosphorylate viral proteins to enhance replication. Given the number of kinase inhibitors that are already FDA approved to treat cancers, fibrosis, and other human disease, they represent an attractive class of compounds to repurpose for host-targeted therapies against emerging coronavirus infections...
August 27, 2023: Journal of Proteome Research
https://read.qxmd.com/read/37399214/smartphone-readable-rpa-lfa-for-the-high-sensitivity-detection-of-leishmania-kdna-using-nanophosphor-reporters
#17
JOURNAL ARTICLE
Adheesha N Danthanarayana, Suman Nandy, Katerina Kourentzi, Binh Vu, Thomas R Shelite, Bruno L Travi, Jakoah Brgoch, Richard C Willson
Early diagnosis of infectious diseases improves outcomes by enabling earlier delivery of effective treatment, and helps prevent further transmission by undiagnosed persons. We demonstrated a proof-of-concept assay combining isothermal amplification and lateral flow assay (LFA) for early diagnosis of cutaneous leishmaniasis, a vector-borne infectious disease that affects ca. 700,000 to 1.2 million people annually. Conventional molecular diagnostic techniques based on polymerase chain reaction (PCR) require complex apparatus for temperature cycling...
July 3, 2023: PLoS Neglected Tropical Diseases
https://read.qxmd.com/read/37360399/target-2035-an-update-on-private-sector-contributions
#18
EDITORIAL
Suzanne Ackloo, Albert A Antolin, Jose Manuel Bartolome, Hartmut Beck, Alex Bullock, Ulrich A K Betz, Jark Böttcher, Peter J Brown, Menorca Chaturvedi, Alisa Crisp, Danette Daniels, Jan Dreher, Kristina Edfeldt, Aled M Edwards, Ursula Egner, Jon Elkins, Christian Fischer, Tine Glendorf, Steven Goldberg, Ingo V Hartung, Alexander Hillisch, Evert Homan, Stefan Knapp, Markus Köster, Oliver Krämer, Josep Llaveria, Uta Lessel, Sven Lindemann, Lars Linderoth, Hisanori Matsui, Maurice Michel, Florian Montel, Anke Mueller-Fahrnow, Susanne Müller, Dafydd R Owen, Kumar Singh Saikatendu, Vijayaratnam Santhakumar, Wendy Sanderson, Cora Scholten, Matthieu Schapira, Sujata Sharma, Brock Shireman, Michael Sundström, Matthew H Todd, Claudia Tredup, Jennifer Venable, Timothy M Willson, Cheryl H Arrowsmith
Target 2035, an international federation of biomedical scientists from the public and private sectors, is leveraging 'open' principles to develop a pharmacological tool for every human protein. These tools are important reagents for scientists studying human health and disease and will facilitate the development of new medicines. It is therefore not surprising that pharmaceutical companies are joining Target 2035, contributing both knowledge and reagents to study novel proteins. Here, we present a brief progress update on Target 2035 and highlight some of industry's contributions...
June 22, 2023: RSC medicinal chemistry
https://read.qxmd.com/read/37307197/intravital-imaging-of-3-different-microvascular-beds-in-sars-cov-2-infected-mice
#19
JOURNAL ARTICLE
Fernanda Vargas E Silva Castanheira, Rita Nguyen, Michelle Willson, Marcela Davoli-Ferreira, Bruna Araujo David, Margaret M Kelly, Woo-Yong Lee, Rachel M Kratofil, Wen Xuan Zhang, Maxwell P Bui-Marinos, Jennifer A Corcoran, Paul Kubes
SARS-CoV-2 enters the respiratory tract where it infects the alveoli epithelial lining. However, patients have sequelae that extend well beyond the alveoli into the pulmonary vasculature and perhaps beyond to brain and other organs. Because of the dynamic events within blood vessels, histology fails to report on platelet and neutrophil dynamics. Because of the rapid non-transcriptional behaviour of these cells neither single-cell RNAseq nor proteomics report robustly on their critical behaviours. We used intravital-microscopy in level-3 containment to examine the pathogenesis of SARS-CoV-2 within three organs in mice expressing human-ACE-2 ubiquitously (CAG-AC-70) or on epithelium (K18-promoter)...
June 12, 2023: Blood Advances
https://read.qxmd.com/read/37258055/bronchodilator-response-by-interrupter-technique-to-guide-management-of-preschool-wheeze
#20
JOURNAL ARTICLE
Paul C Seddon, Rhian Willson, Catherine Olden, Elizabeth Symes, Enrico Lombardi, Nicole Beydon
OBJECTIVE: We examined relationships between clinical features and pulmonary function before and after inhaled corticosteroid (ICS) treatment in wheezy preschool children, and specifically, whether measuring bronchodilator response (BDR) could predict benefit from ICS. DESIGN: Clinical non-randomised intervention study SETTING: Secondary care. PATIENTS: Preschool children (2 years to <6 years) with recurrent wheeze. INTERVENTIONS: Inhaled beta-agonist, ICS...
May 31, 2023: Archives of Disease in Childhood
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